Human Gene CFH (ENST00000367429.9) from GENCODE V44
  Description: Homo sapiens complement factor H (CFH), transcript variant 1, mRNA. (from RefSeq NM_000186)
RefSeq Summary (NM_000186): This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. Mutations in this gene have been associated with hemolytic-uremic syndrome (HUS) and chronic hypocomplementemic nephropathy. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Oct 2011].
Gencode Transcript: ENST00000367429.9
Gencode Gene: ENSG00000000971.17
Transcript (Including UTRs)
   Position: hg38 chr1:196,652,043-196,747,504 Size: 95,462 Total Exon Count: 22 Strand: +
Coding Region
   Position: hg38 chr1:196,652,118-196,747,313 Size: 95,196 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:196,652,043-196,747,504)mRNA (may differ from genome)Protein (1231 aa)
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-  Comments and Description Text from UniProtKB
  ID: CFAH_HUMAN
DESCRIPTION: RecName: Full=Complement factor H; AltName: Full=H factor 1; Flags: Precursor;
FUNCTION: Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway.
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
DISEASE: Genetic variations in CFH are associated with basal laminar drusen (BLD) [MIM:126700]; also known as drusen of Bruch membrane or cuticular drusen or grouped early adult-onset drusen. Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.
DISEASE: Defects in CFH are the cause of complement factor H deficiency (CFHD) [MIM:609814]. A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.
DISEASE: Defects in CFH are a cause of susceptibility to hemolytic uremic syndrome atypical type 1 (AHUS1) [MIM:235400]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.
DISEASE: Genetic variation in CFH is associated with age-related macular degeneration type 4 (ARMD4) [MIM:610698]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin- containing structure known as Bruch membrane.
SIMILARITY: Contains 20 Sushi (CCP/SCR) domains.
SEQUENCE CAUTION: Sequence=CAB41739.1; Type=Frameshift; Positions=341;
WEB RESOURCE: Name=CFHbase; Note=CFH mutation db; URL="http://bioinf.uta.fi/CFHbase/";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CFH";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/cfh/";

-  Primer design for this transcript
 

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: CFH
Diseases sorted by gene-association score: complement factor h deficiency* (1616), hemolytic uremic syndrome, atypical 1* (1307), basal laminar drusen* (1062), macular degeneration, age-related, 4* (1005), atypical hemolytic-uremic syndrome with h factor anomaly* (350), nephrotic syndrome, type 7* (247), cfh-related atypical hemolytic-uremic syndrome* (100), cfh-related dense deposit disease / membranoproliferative glomerulonephritis type ii* (100), hemolytic-uremic syndrome (72), macular degeneration, age-related, 1* (59), membranoproliferative glomerulonephritis (33), retinal drusen (24), choroiditis (23), degeneration of macula and posterior pole (20), central serous chorioretinopathy (18), de novo thrombotic microangiopathy after kidney transplantation* (18), spirochetes disease (17), relapsing fever (16), brain oligodendroglioma (16), lyme disease (15), eye disease (14), thrombotic thrombocytopenic purpura, familial (14), glomerulonephritis (12), thrombotic thrombocytopenic purpura, acquired (11), retinal disease (11), anterior uveitis (10), dense deposit disease (10), kuhnt-junius degeneration (10), multifocal choroiditis (10), hellp syndrome* (9), proliferative glomerulonephritis (9), meningococcal meningitis (8), yemenite deaf-blind hypopigmentation syndrome (8), posterior uveitis (7), catastrophic antiphospholipid syndrome (6), haemophilus influenzae (6), histoplasmosis (5), acute kidney failure (5), clear cell ependymoma (4), nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 247.16 RPKM in Liver
Total median expression: 1578.86 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -17.6075-0.235 Picture PostScript Text
3' UTR -23.40191-0.123 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016060 - Complement_control_module
IPR000436 - Sushi_SCR_CCP

Pfam Domains:
PF00084 - Sushi repeat (SCR repeat)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1FHC - Model 1HAQ - X-ray 1HCC - NMR MuPIT 1HFH - NMR MuPIT 1HFI - NMR MuPIT 1KOV - Model 2BZM - NMR MuPIT 2G7I - X-ray MuPIT 2IC4 - X-ray MuPIT 2JGW - NMR MuPIT 2JGX - NMR MuPIT 2KMS - NMR MuPIT 2QFG - X-ray MuPIT 2QFH - X-ray MuPIT 2RLP - NMR MuPIT 2RLQ - NMR MuPIT 2UWN - X-ray MuPIT 2V8E - X-ray MuPIT 2W80 - X-ray MuPIT 2W81 - X-ray MuPIT 2WII - X-ray MuPIT 2XQW - X-ray MuPIT 3GAU - X-ray 3GAV - X-ray 3GAW - X-ray 3KXV - X-ray MuPIT 3KZJ - X-ray MuPIT 3OXU - X-ray MuPIT 3R62 - X-ray MuPIT 3RJ3 - X-ray MuPIT 3SW0 - X-ray MuPIT 4B2R - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P08603
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0008201 heparin binding
GO:0043395 heparan sulfate proteoglycan binding

Biological Process:
GO:0002376 immune system process
GO:0006956 complement activation
GO:0006957 complement activation, alternative pathway
GO:0016032 viral process
GO:0030449 regulation of complement activation
GO:0045087 innate immune response

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0070062 extracellular exosome
GO:0072562 blood microparticle


-  Descriptions from all associated GenBank mRNAs
  AK291395 - Homo sapiens cDNA FLJ75416 complete cds, highly similar to Homo sapiens complement factor H (CFH), mRNA.
Y00716 - Human mRNA for complement factor H.
BC142699 - Homo sapiens complement factor H, mRNA (cDNA clone MGC:165027 IMAGE:40148771), complete cds.
AK226113 - Homo sapiens mRNA for complement factor H isoform a precursor variant, clone: hg03448.
M17517 - Human complement H factor mRNA, complete cds.
AK225649 - Homo sapiens mRNA for complement factor H isoform b precursor variant, clone: STM02757.
X07523 - Human mRNA for truncated form of complement factor H.
BC037285 - Homo sapiens complement factor H, mRNA (cDNA clone IMAGE:5267249), complete cds.
BC012610 - Homo sapiens complement factor H, mRNA (cDNA clone IMAGE:3996233).
BC110643 - Homo sapiens complement factor H, mRNA (cDNA clone IMAGE:4512906), complete cds.
BC073982 - Homo sapiens cDNA clone IMAGE:6189000, containing frame-shift errors.
JD173772 - Sequence 154796 from Patent EP1572962.
CU691466 - Synthetic construct Homo sapiens gateway clone IMAGE:100019454 5' read CFH mRNA.
JF432152 - Synthetic construct Homo sapiens clone IMAGE:100073298 complement factor H (CFH) gene, encodes complete protein.
KJ896967 - Synthetic construct Homo sapiens clone ccsbBroadEn_06361 CFH gene, encodes complete protein.
KR710733 - Synthetic construct Homo sapiens clone CCSBHm_00016334 CFH (CFH) mRNA, encodes complete protein.
KR710734 - Synthetic construct Homo sapiens clone CCSBHm_00016336 CFH (CFH) mRNA, encodes complete protein.
KR710735 - Synthetic construct Homo sapiens clone CCSBHm_00016341 CFH (CFH) mRNA, encodes complete protein.
KR710736 - Synthetic construct Homo sapiens clone CCSBHm_00016342 CFH (CFH) mRNA, encodes complete protein.
X04697 - Human mRNA for complement factor H 38-kDa N-terminal fragment.
M12383 - Human complement protein H mRNA, 3' end.
M65294 - Human factor H homologue mRNA, 3' end.
JD062107 - Sequence 43131 from Patent EP1572962.
JD552627 - Sequence 533651 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04610 - Complement and coagulation cascades

Reactome (by CSHL, EBI, and GO)

Protein P08603 (Reactome details) participates in the following event(s):

R-HSA-976768 Factor H binds to C3b
R-HSA-1006169 Factor H binds host cell surface markers
R-HSA-976743 Factor I inactivates plasma Factor H-bound C3b
R-HSA-976810 Complement factor I binds to extracellular Factor H:C3b
R-HSA-977363 Factor H binds to C3bBb
R-HSA-981728 Factor H binds to membrane-associated C3b
R-HSA-977605 Factor H displaces Bb
R-HSA-977359 Complement factor I binds to membrane-associated Factor H:C3b
R-HSA-977371 Factor I inactivates Factor H-boundC3b
R-HSA-977606 Regulation of Complement cascade
R-HSA-166658 Complement cascade
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A5PL14, CFAH_HUMAN, ENST00000367429.1, ENST00000367429.2, ENST00000367429.3, ENST00000367429.4, ENST00000367429.5, ENST00000367429.6, ENST00000367429.7, ENST00000367429.8, HF, HF1, HF2, NM_000186, P08603, P78435, Q14570, Q2TAZ5, Q38G77, Q5TFM3, Q8N708, Q9NU86, uc001gtj.1, uc001gtj.2, uc001gtj.3, uc001gtj.4, uc001gtj.5
UCSC ID: ENST00000367429.9
RefSeq Accession: NM_000186
Protein: P08603 (aka CFAH_HUMAN)
CCDS: CCDS1385.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene CFH:
husa (Genetic Atypical Hemolytic-Uremic Syndrome)
mpgn (C3 Glomerulopathy)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.